Synthesis and antimalarial activity of new heterocyclic hybrids based on chloroquine and thiazolidinone scaffolds

A series of new 21 chloroquine heterocyclic hybrids containing either benzylamino fragment or N-(aminoalkyl)thiazolidin-4-one moiety were synthesized and screened for their antimalarial activity against chloroquine (CQ)-sensitive 3D7 and multidrug-resistance Dd2 strains of Plasmodium falciparum. Although no compounds more active than CQ against 3D7 was found; against Dd2 strain, six compounds, four of them with benzylamino fragment, showed an excellent activity, up to 3-fold more active than CQ. Non specific cytotoxicity on J774 macrophages was observed in some compounds whereas only two of them showed liver toxicity on HepG2 cells. In addition, all active compounds inhibited the ferriprotoporphyrin IX biocrystalization process in concentrations around to CQ. In vivo preliminary results have shown that at least two compounds are as active as CQ against Plasmodium berghei ANKA.

A series of new 21 chloroquine molecules 1–4, 8–24 were synthesized and screened for their antimalarial activity against chloroquine (CQ)-sensitive 3D7 and multidrug-resistance Dd2 strains of Plasmodium falciparum. Six compounds, four of them with benzylamino fragment, showed an excellent activity against Dd2 strain, up to 3-fold more active than CQ. In vivo preliminary results have shown that two compounds 19 and 23 are as active as CQ against Plasmodium berghei ANKA.Figure optionsDownload as PowerPoint slide